Real-World Outcomes in Patients With Brain Metastases Secondary to HER2-Positive Breast Cancer: An Australian Multi-centre Registry-based Study

• Published in: Clinical breast cancer 2022-10, Vol.22 (7), p.e764-e772
• Main Authors: Tung, Iris, Moldovan, Cristina, Wong, Vanessa, De Boer, Richard, Yeo, Belinda, Malik, Laeeq, Greenberg, Sally, Anton, Angelyn, Nott, Louise, Barnett, Frances, Collins, Ian M, Lombard, Janine, Nottage, Michelle, Sahu, Arvind, Torres, Javier, Gibbs, Peter, Lok, Sheau Wen
• Format: Article
• Language: English
• Subjects: Chemotherapy; Intracranial; Local therapy; TABITHA; Targeted therapy
• ISSN: 1526-8209; 1938-0666
• DOI: 10.1016/j.clbc.2022.07.005

The development of brain metastases occurs commonly in HER2-positive metastatic breast cancer and is associated with a poorer prognosis. The advent of HER2-targeted therapy has improved overall survival, but the benefit in patients with brain metastases is unclear, as these patients are often excluded from clinical trials. This study aimed to explore real-world outcomes in patients with brain metastases in HER2-positive MBC. Data was extracted from the TABITHA registry, which consists of patient data collected prospectively from 16 Australian sites from 24th February 2015 to 31st October 2021. Data analysed included characteristics of brain metastases, treatment received and survival outcomes. A total of 135 (37%) of 361 patients with HER2-positive MBC were diagnosed with brain metastases during their clinical course, including 45 (12%) with brain metastases at time of MBC diagnosis. 61 (45%) had ≥4 brain lesions. The most common local therapy given was whole brain radiation therapy (WBRT) (36%) followed by multi-modality treatment with both surgery and radiation therapy (27%). The majority of patients received first-line HER2-targeted treatment with trastuzumab and pertuzumab followed by second-line trastuzumab emtansine (T-DM1) but third-line therapy was heterogenous. The median overall survival in patients who developed brain metastases was significantly shorter than those who did not develop brain metastases (58.9 vs. 96.1 months, P = .02). Real-world patients diagnosed with brain metastases in HER2-positive MBC have a relatively poor prognosis, despite advances in HER2-targeted treatment. As the range of HER2-targeted treatment expands, it is important to pursue clinical trials that focus on patients with brain metastases. Despite advances in HER2-targeted therapy, real-world patients with brain metastases secondary to HER2-positive metastatic breast cancer had a significantly shorter overall survival of 58.9 months versus 96.1 months in those who never developed brain metastases. As newer HER2-targeted agents become available, it is important to pursue clinical trials that focus on patients with brain metastases.